Down syndrome is one of the most common inborn causes of intellectual disability. Down syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21.
In addition to various physical characteristics, Down syndrome is often, though not always, characterized by varying degrees of cognitive impairment, impairment in memory, learning capacity or both. While advances in teaching methods and a trend toward educational mainstreaming has led to an improvement in cognitive development in those who have Down syndrome, there remain constitutive impairments that cannot be fully addressed through pedagogic methodology alone.
Attempts at elaborating drugs for enhancing cognitive function in Down syndrome patients have been made. For example, piracetam is widely used as a purported means of improving cognitive function in children with Down syndrome. However, neither cognitive nor behavioral measures demonstrated improvement under piracetam, even at doses associated with adverse effects (Lobaugh N J et al. Arch Pediatr Adolesc Med. 2001; 155(4):442-448).
WO 2011/086126 A1 discloses a compound which inhibits the importation of chloride into neurons or a compound which improve the outflow of chloride from neurons for use in the treatment of autism; more specifically, the compound claimed is a diuretic and, in particular, bumetanide.
EP2298296 discloses the use of inverse agonist for GABAA receptors to enhance cognitive function.
Despite continued work, no notable medical treatments for Down syndrome have been forthcoming. Therefore, there is a need for alternative targets to improve cognitive/memory deficits related to Down syndrome.
The present invention thus relates to the use of a modulator of intracellular chloride levels, in particular inhibitor of chloride transporters for treating Down syndrome in a subject in need thereof.